Drugs are administered by several routes, including subcutaneously, orally, intramuscular, intravenously, and transdermally. Each of these approaches includes drawbacks when considering the effectiveness and side effects of the drug. With the blood-brain barrier serving to keep unwanted substances out of the brain, current methods of administering anesthesia and certain other drugs require that a very large dose of the compound be injected into the blood stream so that the drug is received by the brain. As the drug travels throughout the body, the drug may be absorbed by parts of the body not intended to intended to be exposed to the drug, sometimes resulting in severe and adverse side effects.
Oral ingestion wastes drugs because of the passage of the drugs through the digestive system, in addition to the drugs being subject to first-pass metabolism where there is a reduced effectiveness caused by liver enzymes. In addition, these compounds may take a long time to produce the desired effect when administered orally.
Injection allows therapeutic agents to bypass the effects of metabolism, but injections are painful and carry the risk of infection, besides producing large amounts of hazardous waste, e.g., used needles contaminated with body fluid.
In addition to the drawbacks described elsewhere herein, conventional methods administer drugs in locations that are remote from the brain, where portions of the pharmacological effects are realized in the body, though the desired effect is in the brain.
In order to remove dependence on needles and invasive administration, a method of transdermally introducing chemical compounds into the bloodstream via intact skin is known. Transdermal administration delivers drugs or other chemicals through the skin to local tissue, and then into the systemic circulatory system without cutting or penetration of the skin. Using transdermal methods rather than injections reduces pain, biohazardous waste, and risk of infection. Currently, transdermal delivery systems have been proposed or developed for a variety of drugs or therapeutic agents to treat many conditions and diseases.
While transdermal delivery of drugs presents many potential benefits and wide applications, its development is limited due to the biological nature of the skin, which presents a barrier to penetration because the low permeability of the skin limits the application of transdermal delivery. The transdermal flux of a drug depends on the diffusion coefficient of the drug; the thickness of the epidermis and dermis, and the condition of the skin at the application site; and the concentration gradient across the skin.
Passive transdermal delivery methods comprise the use of patches that contain a drug, and often a permeation enhancer. The structure of transdermal delivery patches generally comprises an outer layer, a middle layer that contains the drug, and a liner and/or a release liner that protects the adhesive layer, which is removed prior to use.
As briefly described above, transdermal delivery of active agents is generally executed in an area of the body that is remote from the brain or active control center that is affected by the drug being introduced into the body such as, for example, the arm, buttock, back, or leg. All of the areas currently used for transdermal delivery have a great deal of adipose tissue, i.e., fat, which serves as a significant barrier to transdermal delivery of therapeutic agents. These sites present limitations to the transdermal delivery methods, as a high dosage must be used to ensure that an effective dose reaches the control center designed to be treated by the drug. Excess drugs and active agents circulating throughout the body may be absorbed by organs and tissues not intended to be treated, thus resulting in an increased risk for damaging side effects. For this reason especially, transdermal delivery is extremely limited or impossible for use with potent drugs.